The present invention is directed generally to method for diagnosing and treating a patient with emphysema or COPD and more particularly to methods for diagnosing and treating a patient with emphysema or COPD by detecting the presence of EMAP II and neutralizing EMAP II.
Over 3.1 million Americans have been diagnosed with emphysema. Emphysema and chronic bronchitis are the two components of the syndrome of chronic obstructive pulmonary disease (COPD). COPD is the fourth leading cause of death in America. (See www.nhlbi.nih.gov/health/public/lung/other/copd_fact. htm#toc). This disease has no effective treatment that reverses its course or halts its progression.
Pulmonary emphysema is a prevalent fatal disease, characterized by loss of both matrix and cellular elements of the lung, thus impairing gas exchange between the alveolar space and the capillary blood. Emphysema is defined as “a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, with or without obvious fibrosis”. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases workshop, Am Rev Respir Dis 132, 182-185. (1985). The concepts of permanent and destruction are critical in this definition as they convey the unique and characteristic distinguishing features of a disease process ultimately leading to the disappearance of lung tissue.
Although the environmental inducers in susceptible individuals have been identified, the mechanisms by which these initiate a loss of alveoli leading to emphysema are poorly understood. Over the past decades, inflammation and a protease/antiprotease imbalance have been proposed to act as downstream effectors of the lung destruction following chronic cigarette smoking, which accounts for most cases of emphysema. Pro-inflammatory stimuli are postulated to recruit and activate lung inflammatory cells, triggering matrix protease release and lung remodeling. Shapiro, S. D., J Clin Invest 106, 1309-1310 (2000). However, these models fail to fully account for the mechanisms behind the eradication of septal structures and the unique nature of lung destruction as compared to alterations seen in other inflammatory lung diseases. To account for the permanent destruction seen in emphysema, excessive apoptosis of structural alveolar cells have emerged as a second major mechanism of emphysema. Excessive alveolar endothelial apoptosis is thought to cause capillary regression, with subsequent loss of alveolar wall. Tuder, R. M. et al., Am J Respir Cell Mol Biol 28, 551-554 (2003). However, the coexistence of an excessive lung structural cell apoptosis with that of an activated inflammatory state in emphysema and the hierarchy of these two mechanisms have not yet been explained.
As can be seen, there is a need for a method for treating pulmonary emphysema. There is also a need for a method for diagnosing pulmonary emphysema in the early stages. Early diagnosis and subsequent treatment may result in more effective treatment of the disease and a better prognosis for the patient.